Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C.

Johannes Wiegand, Markus Cornberg, Nuray Aslan, Verena Schlaphoff, Christoph Sarrazin, Anne Kubitschke, Peter Buggisch, Ayse Ciner, Elmar Jaeckel, Michael P Manns, Heiner Wedemeyer

Journal: Antiviral therapy 2007;12(3):303-16

PMID: 17591020

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Abstract

BACKGROUND

Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity.

METHODS

T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-alpha2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers.

RESULTS

HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4+ and CD8+ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8+ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8+ T-cells by week 12.

CONCLUSIONS

Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.

Address: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.

Link outs

Free resources

Medical:

https://medlineplus.gov/hepatitisc.html

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-HLA-DQA1...

MeSH Terms: Acute Disease, Adult, Aged, Amino Acid Sequence, Annexin A5, Antiviral Agents, Binding Sites, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte, Female, Flow Cytometry, HLA-A2 Antigen, Hepacivirus, Hepatitis C, Humans, Interferon alpha-2, Interferon-alpha, Lymphocyte Count, Male, Molecular Sequence Data, Polyethylene Glycols, RNA, Viral, Receptors, CXCR3, Receptors, Chemokine, Recombinant Proteins, Species Specificity, Treatment Outcome